Top 10 Most Influential Articles on FT-IR Spectroscopy in Biopharmaceutical Applications during 2024–2025

Abstract

Between 2024 and 2026, FT-IR spectroscopy has transitioned from a largely confirmatory analytical tool to a quantitative, predictive, and process-integrated technology for biopharmaceutical analysis. This review summarizes ten highly influential publications that demonstrate FT-IR applications in solid-state engineering, coamorphous systems, bioprocess monitoring, green nanotechnology, drug discovery, machine learning–assisted clinical analysis, and hyphenated chromatographic techniques. Collectively, these studies highlight FT-IR’s expanding analytical relevance and its integration with chemometrics and artificial intelligence (AI) to support modern biopharmaceutical development and manufacturing.

Introduction

Biopharmaceutical products pose substantial analytical challenges due to molecular complexity, polymorphism, and strict regulatory expectations for quality and consistency. FT-IR spectroscopy has long provided rapid molecular insight through vibrational absorption signatures, but recent methodological and computational advances have dramatically extended its capabilities. Over the 2024–2026 period, FT-IR has become increasingly embedded in quantitative modeling, in-line monitoring, and data-driven decision frameworks. The ten papers reviewed below represent some of the most influential contributions during this period, selected for their methodological innovation, impact on biopharmaceutical practice, and broad citation and adoption.

1. FT-IR in Cocrystal Engineering for Bioavailability Enhancement

Suryawanshi et al. reported the design and characterization of a quercetagetin–betaine–ethanol cocrystal system, using FT-IR spectroscopy to confirm hydrogen bonding interactions critical to supramolecular assembly (1). FT-IR data provided direct evidence of hydroxyl–carboxylate interactions, supporting crystallographic and thermal analyses.
This paper is influential because it demonstrates FT-IR’s essential role in mechanistically validating crystal engineering strategies that directly translate into improved aqueous solubility and in vivo bioavailability of biopharma substances. The paper exemplifies how FT-IR spectroscopy enables rational solid-state design rather than serving solely as a supporting characterization or quality tool.

2. Foundational FT-IR Methodology Applied to Bioactive Compounds

Kumar et al. presented a comprehensive tutorial chapter on FT-IR spectroscopy with practical case studies involving natural and synthetic bioactive compounds (2). The chapter bridges fundamental vibrational theory discussions with real-world pharmaceutical and biopharmaceutical applications.
The paper’s influence arises from its role as a unifying reference that standardizes FT-IR interpretation practices for bioactive and biopharmaceutical compounds. The chapter has been widely cited for training new practitioners and reinforcing best practices across academic and industrial laboratories.

3. FT-IR within Real-Time Bioprocess Monitoring Frameworks

Mishra et al. reviewed advances in vibrational and fluorescence spectroscopy for real-time bioprocess monitoring, highlighting FT-IR as a cost-effective process analytical technology (PAT) tool for upstream and fermentation processes (3).

This review is influential because it positions FT-IR as a practical, scalable solution within modern PAT and factory acceptance testing (FAT) frameworks. By comparing FT-IR with alternative spectroscopic techniques, the paper helped clarify its unique value proposition for real-time bioprocess analytics.

4. ATR FT-IR Platforms for Upstream Bioprocess Analytics

Christie et al. evaluated an innovative attenuated total reflectance (ATR) FT-IR platform employing disposable internal reflection elements for upstream bioprocess monitoring (4). Multivariate models enabled accurate quantification of glucose and lactic acid and differentiation of cellular health states.

The study is influential due to its demonstration of Good Manufacturing Practice (GMP)-compatible FT-IR hardware innovation. The disposable ATR approach significantly lowers contamination and maintenance barriers, accelerating industrial adoption of FT-IR-based PAT systems.

5. FT-IR in Green-Synthesized Nanoparticles Relevant to Biopharma

Pasieczna-Patkowska et al. reviewed FT-IR spectroscopy for characterizing green-synthesized nanoparticles, focusing on functional groups responsible for reduction, capping, and stabilization (5).
Although metal nanoparticles have limited direct systemic use, this paper is influential because it consolidates FT-IR interpretation strategies applicable to lipid nanoparticles, polymeric carriers, and biologically derived nanomaterials increasingly used in biopharmaceutical delivery systems.

6. FT-IR as a Core Tool in Drug Discovery Spectroscopy

Kumar et al. examined the integrated use of FT-IR, Raman, and NIR spectroscopy in drug discovery workflows, emphasizing FT-IR’s role in functional group identification and molecular interaction analysis (6).

This work is influential because it situates FT-IR within high-throughput, data-rich discovery pipelines, reinforcing its relevance in early-stage pharmaceutical and biopharmaceutical development alongside complementary vibrational techniques.

7. FT-IR, Coamorphous Systems, and AI-Driven Formulation Design

Khemchandani et al. combined FT-IR spectroscopy with density functional theory (DFT) calculations, molecular dynamics simulations, and machine learning (ML) to design and characterize coamorphous drug systems (7). FT-IR data were central to identifying intermolecular interactions used as predictive descriptors.

This paper is influential because it exemplifies the convergence of FT-IR spectroscopy with artificial intelligence (AI). It elevates FT-IR from descriptive analysis to a source of predictive features for formulation design decisions and stability modeling.

8. Machine Learning–Assisted FT-IR Analysis of Blood Serum

Chechekina et al. demonstrated that FT-IR spectra of blood serum, combined with regression and machine learning models, can accurately predict multiple biochemical parameters (8).

The study is influential due to its clinical relevance and strong quantitative performance. It expands FT-IR’s biopharmaceutical impact into diagnostics and therapeutic monitoring, highlighting its potential for rapid, minimally invasive biochemical assessment.

9. Hyphenated HPLC–FT-IR for Complex Biopharmaceutical Mixtures

Halko et al. provided a comprehensive review of high performance liquid chromatography (HPLC)–FT-IR coupling, critically assessing interface designs, solvent elimination strategies, and analytical limitations (9).
This review is influential because it revives attention to a powerful yet underutilized hyphenated technique. It emphasizes FT-IR’s unmatched chemical specificity for post-separation identification in complex biopharmaceutical mixtures.

10. Quantitative Polymorph Analysis Using FT-IR Imaging and Chemometrics

Yang et al. compared powder X-ray diffraction (PXRD), FT-IR, and Raman spectroscopy for quantitative polymorph analysis of resmetirom in active pharmaceutical ingredients (APIs) and formulations, demonstrating the effectiveness of FT-IR for polymorph analysis when paired with multivariate analysis (10).
This paper is influential because it confirms that FT-IR spectroscopy can deliver regulatory-relevant quantitative performance in solid-state analysis when combined with appropriate chemometric preprocessing and modeling strategies.

Final Summary

The ten studies reviewed here collectively illustrate the transformation of FT-IR spectroscopy into a quantitative, predictive, and process-integrated analytical technology for decision-making for biopharmaceutical applications. Advances in instrumentation, data analytics, and hybrid methodologies have substantially expanded FT-IR’s analytical impact.

Conclusion

From solid-state engineering and formulation science to bioprocess monitoring, nanotechnology, clinical diagnostics, and hyphenated separations, FT-IR spectroscopy has emerged as a cornerstone analytical tool in biopharmaceutical science during 2023–2026. The influence of these ten papers reflects a broader shift toward data-driven, model-enabled spectroscopy that aligns with modern regulatory and manufacturing expectations.

References

(1) Suryawanshi, S.; Shaligram, P.; Gonnade, R. G.; et al. Novel Cocrystal of Quercetagetin: In Vitro and In Vivo Insights into Biopharmaceutical Performance. Pharm. Res. 2026. DOI: 10.1007/s11095-026-04019-1.

(2) Kumar, S.; Seema, M. T.; Gulia, S.; Sindhu, R. K.; Priya, A. Fourier Transform Infrared Spectroscopy (FTIR) and Its Application in Characterization and Identification of Natural Products. In Handbook of Natural Bioactive Compounds: Extraction, Isolation and Identification; 2026; pp 411–430.

(3) Mishra, A.; Aghaee, M.; Tamer, I. M.; Budman, H. Spectroscopic Advances in Real-Time Monitoring of Pharmaceutical Bioprocesses. Spectrosc. J. 2025, 3(2), 12. DOI: 10.3390/spectroscj3020012.

(4) Christie, L.; Rutherford, S.; Palmer, D. S.; Baker, M. J.; Butler, H. J. Bioprocess Monitoring Applications of an Innovative ATR-FTIR Spectroscopy Platform. Front. Bioeng. Biotechnol. 2024, 12, 1349473. DOI: 10.3389/fbioe.2024.1349473.

(5) Pasieczna-Patkowska, S.; Cichy, M.; Flieger, J. Application of FTIR Spectroscopy in Characterization of Green Synthesized Nanoparticles. Molecules 2025, 30(3), 684. DOI: 10.3390/molecules30030684.

(6) Kumar, N.; Sharma, G.; Sharma, A.; et al. Recent Uses of FT-IR, Raman, and NIR Spectroscopy in Drug Discovery. In Modern Spectroscopic Techniques for Drug Discovery and Environmental Sustainability; IGI Global: 2025; pp 133–150. DOI: 10.4018/979-8-3693-7473-3.ch006.

(7) Khemchandani, R.; Pardhi, E.; Jadhav, A.; et al. Integrated Experimental, Computational and Machine Learning Approaches for the Development of Apremilast-Aceclofenac Coamorphous Systems. Int. J. Pharm. 2025, 686, 126283. DOI: 10.1016/j.ijpharm.2025.126283.

(8) Chechekina, O. G.; Tropina, E. V.; Fatkhutdinova, L. I.; et al. Machine learning Assisted Rapid Approach for Quantitative Prediction of Biochemical Parameters of Blood Serum With FTIR Spectroscopy. Spectrochim. Acta A 2025, 326, 125283. DOI: 10.1016/j.saa.2024.125283.

(9) Halko, R.; Pavelek, D.; Kaykhaii, M. High-Performance Liquid Chromatography–Fourier Transform Infrared Spectroscopy Coupling: A Comprehensive Review. Crit. Rev. Anal. Chem. 2026, 56(1), 167–178. DOI: 10.1080/10408347.2024.2391892

(10) Yang, C.; Luo, Y.; Sun, W.; Liu, X.; Zhu, X. Comparison of Resmetirom Quantitative Analysis in API and Formulation Models Based on PXRD, FTIR and Raman Scanning Imaging Combined with Univariate and Multivariate Analyses. Talanta 2025, 287, 127568. DOI: 10.1016/j.talanta.2025.127568